F2RL1 - Proteinase-activated receptor 2 - human protein (Function)
 
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F2RL1 »  Proteinase-activated receptor 2  (PAR-2)
 
Protein also known as:  Coagulation factor II receptor-like 1. Cleaved into:  Proteinase-activated receptor 2, alternate cleaved 1; Proteinase-activated receptor 2, alternate cleaved 2.
Gene name:  F2RL1
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

 show evidences
Overview 
Receptor for trypsin and trypsin-like enzymes coupled to G proteins. Its function is mediated through the activation of several signaling pathways including phospholipase C (PLC), intracellular calcium, mitogen-activated protein kinase (MAPK), I-kappaB kinase/NF-kappaB and Rho. Can also be transactivated by cleaved F2R/PAR1. Involved in modulation of inflammatory responses and regulation of innate and adaptive immunity, and acts as a sensor for proteolytic enzymes generated during infection. Generally is promoting inflammation. Can signal synergistically with TLR4 and probably TLR2 in inflammatory responses and modulates TLR3 signaling. Has a protective role in establishing the endothelial barrier; the activity involves coagulation factor X. Proposed to have a bronchoprotective role in airway epithelium, but also shown to compromise the airway epithelial barrier by interrupting E-cadherin adhesion. Involved in the regulation of vascular tone; activation results in hypotension presumably mediated by vasodilation. Associates with a subset of G proteins alpha subunits such as G alpha-q, G alpha-11, G alpha-14, G alpha-12 and G alpha-13, but probably not with G(o) alpha, G(i) subunit alpha-1 and G(i) subunit alpha-2. However, according to PubMed21627585 can signal through G(i) subunit alpha. Believed to be a class B receptor which internalizes as a complex with arrestin and traffic with it to endosomal vesicles, presumably as desensitized receptor, for extended periods of time. Mediates inhibition of TNF-alpha stimulated JNK phosphorylation via coupling to G alpha-q/11; the function involves dissociation of RIPK1 and TRADD from TNFR1. Mediates phosphorylation of nuclear factor NF-kappa-B RELA subunit at 'Ser-536'; the function involves IKBKB and is predominantly independent of G proteins. Involved in cellular migration. Involved in cytoskeletal rearrangement and chemotaxis through beta-arrestin-promoted scaffolds; the function is independent of G alpha-q/11 and involves promotion of cofilin dephosphoryltaion and actin filament severing. Induces redistribution of COPS5 from the plasma membrane to the cytosol and activation of the JNK cascade is mediated by COPS5. Involved in the recruitment of leukocytes to the sites of inflammation and is the major PAR receptor capable of modulating eosinophil function such as proinflammatory cytokine secretion, superoxide production and degranulation. During inflammation promotes dendritic cell maturation, trafficking to the lymph nodes and subsequent T-cell activation. Involved in antimicrobial response of innate immnune cells; activation enhances phagocytosis of Gram-positive and killing of Gram-negative bacteria. Acts synergistically with interferon-gamma in enhancing antiviral responses. Implicated in a number of acute and chronic inflammatory diseases such as of the joints, lungs, brain, gastrointestinal tract, periodontium, skin, and vascular systems, and in autoimmune disorders.  
25
  • CuratedUniProtKB
GO molecular function 
G-protein alpha-subunit bindingdefinition[GO:0001965]  
  • ISSOrtholog Curator
G-protein beta-subunit bindingdefinition[GO:0031681]  
  • ISSOrtholog Curator
G-protein coupled receptor activitydefinition[GO:0004930]  
1
  • IMPUniProtKB
  • ISSOrtholog Curator
Protein bindingdefinition[GO:0005515]  
5
  • IPIIntAct
Receptor activitydefinition[GO:0004872]  
1
  • TASPINC
Receptor bindingdefinition[GO:0005102]  
1
  • TASPINC
Thrombin receptor activitydefinition[GO:0015057] silver  
  • IEAInterPro 2 GO
GO biological process 
Blood coagulationdefinition[GO:0007596] silver  
  • IEAInterPro 2 GO
Chemokine (C-C motif) ligand 2 secretiondefinition[GO:0035926]  
1
  • IDAUniProtKB
Chemokine secretiondefinition[GO:0090195]  
2
  • IDAUniProtKB
Defense response to virusdefinition[GO:0051607]  
2
  • IDAUniProtKB
Establishment of endothelial barrierdefinition[GO:0061028]  
1
  • IDAUniProtKB
G-protein coupled receptor signaling pathwaydefinition[GO:0007186]  
1
  • TASPINC
Inflammatory responsedefinition[GO:0006954]  
  • IEAUniProtKB KW
Innate immune responsedefinition[GO:0045087]  
  • IEAUniProtKB KW
Interferon-gamma secretiondefinition[GO:0072643]  
  • ISSOrtholog Curator
Interleukin-1 beta secretiondefinition[GO:0050702]  
1
  • IDAUniProtKB
Interleukin-10 secretiondefinition[GO:0072608]  
1
  • IDAUniProtKB
Leukocyte migrationdefinition[GO:0050900]  
1
  • IDAUniProtKB
Leukocyte proliferationdefinition[GO:0070661]  
  • ISSOrtholog Curator
Mature dendritic cell differentiationdefinition[GO:0097029]  
1
  • IDAUniProtKB
  • ISSOrtholog Curator
Negative regulation of chemokine secretiondefinition[GO:0090198]  
1
  • IDAUniProtKB
Negative regulation of JNK cascadedefinition[GO:0046329]  
1
  • IDAUniProtKB
Negative regulation of toll-like receptor 3 signaling pathwaydefinition[GO:0034140]  
1
  • IMPUniProtKB
Negative regulation of tumor necrosis factor-mediated signaling pathwaydefinition[GO:0010804]  
1
  • IDAUniProtKB
Neutrophil activationdefinition[GO:0042119]  
1
  • IDAUniProtKB
Positive regulation of actin filament depolymerizationdefinition[GO:0030836]  
1
  • IDAUniProtKB
Positive regulation of cell migrationdefinition[GO:0030335]  
  • ISSOrtholog Curator
Positive regulation of chemotaxisdefinition[GO:0050921]  
  • ISSOrtholog Curator
Positive regulation of cytokine secretion involved in immune responsedefinition[GO:0002741]  
1
  • IDAUniProtKB
Positive regulation of cytosolic calcium ion concentrationdefinition[GO:0007204]  
1
  • IDAUniProtKB
  • ISSOrtholog Curator
Positive regulation of eosinophil degranulationdefinition[GO:0043311]  
1
  • IDAUniProtKB
Positive regulation of ERK1 and ERK2 cascadedefinition[GO:0070374]  
1
  • IDAUniProtKB
  • ISSOrtholog Curator
Positive regulation of glomerular filtrationdefinition[GO:0003104]  
  • ISSOrtholog Curator
Positive regulation of I-kappaB kinase/NF-kappaB signalingdefinition[GO:0043123]  
1
  • IDAUniProtKB
Positive regulation of interleukin-6 secretiondefinition[GO:2000778]  
2
  • IDAUniProtKB
Positive regulation of interleukin-8 secretiondefinition[GO:2000484]  
4
  • IDAUniProtKB
Positive regulation of JNK cascadedefinition[GO:0046330]  
1
  • IDAUniProtKB
Positive regulation of leukocyte chemotaxisdefinition[GO:0002690]  
1
  • IDABHF-UCL
Positive regulation of neutrophil mediated killing of gram-negative bacteriumdefinition[GO:0070963]  
1
  • IDAUniProtKB
Positive regulation of phagocytosis, engulfmentdefinition[GO:0060100]  
1
  • IDAUniProtKB
Positive regulation of phosphatidylinositol 3-kinase signalingdefinition[GO:0014068]  
  • ISSOrtholog Curator
Positive regulation of positive chemotaxisdefinition[GO:0050927]  
1
  • IDABHF-UCL
Positive regulation of pseudopodium assemblydefinition[GO:0031274]  
  • ISSOrtholog Curator
Positive regulation of renin secretion into blood streamdefinition[GO:1900135]  
  • ISSOrtholog Curator
Positive regulation of Rho protein signal transductiondefinition[GO:0035025]  
1
  • IMPUniProtKB
  • ISSOrtholog Curator
Positive regulation of superoxide anion generationdefinition[GO:0032930]  
1
  • IDAUniProtKB
Positive regulation of toll-like receptor 2 signaling pathwaydefinition[GO:0034137]  
1
  • IMPUniProtKB
Positive regulation of toll-like receptor 3 signaling pathwaydefinition[GO:0034141]  
1
  • IMPUniProtKB
Positive regulation of toll-like receptor 4 signaling pathwaydefinition[GO:0034145]  
1
  • IDAUniProtKB
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944]  
1
  • IDAUniProtKB
Positive regulation of vasodilationdefinition[GO:0045909]  
  • ISSOrtholog Curator
Regulation of blood coagulationdefinition[GO:0030193]  
1
  • IDABHF-UCL
Regulation of I-kappaB kinase/NF-kappaB signalingdefinition[GO:0043122]  
1
  • IDAUniProtKB
Regulation of JNK cascadedefinition[GO:0046328]  
1
  • IDAUniProtKB
T cell activation involved in immune responsedefinition[GO:0002286]  
  • ISSOrtholog Curator
Pathways 
According to KEGG, this protein belongs to the following pathways:
African trypanosomiasis  hsa05143+2150  
Neuroactive ligand-receptor interaction  hsa04080+2150  
According to Reactome, this protein belongs to the following pathway:
Signal Transduction  REACT_111102  
 

Keywords

Biological process 
Immunity  definition   [KW-0391]
Inflammatory response  definition   [KW-0395]
Innate immunity  definition   [KW-0399]
Molecular function 
G-protein coupled receptor  definition   [KW-0297]
Receptor  definition   [KW-0675]
Transducer  definition   [KW-0807]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: Protease_activated_receptor_2
GenomeRNAi: 2150
PRO: PR:P55085
Chemistry
GuidetoPHARMACOLOGY: 348